Lourdes Garrido-Sánchez

Oxidative Stress in Severely Obese Persons Is Greater in Those With Insulin Resistance

The postprandial state seems to have a direct influence on oxidative status and insulin resistance. We determined the effect of an increase in plasma triglycerides after a high‐fat meal on oxidative stress in severely obese patients with differing degrees of insulin resistance. The study was undertaken in 60 severely obese persons who received a 60‐g fat overload with a commercial preparation. Measurements were made of insulin resistance, the plasma activity of various antioxidant enzymes, the total antioxidant capacity (TAC) and the plasma concentration of thiobarbituric acid reactive substances (TBARS). The patients with greater insulin resistance had a lower plasma superoxide dismutase (SOD) activity (P < 0.05) and a greater glutathione peroxidase (GSH‐Px) activity (P < 0.05). The high‐fat meal caused a significant reduction in SOD activity and an increase in the plasma concentration of TBARS in all the patients. Only the patients with lower insulin resistance experienced a significant increase in plasma catalase activity (2.22 ± 1.02 vs. 2.93 ± 1.22 nmol/min/ml, P < 0.01), remaining stable in the patients with greater insulin resistance. These latter patients had a reduction in plasma TAC (6.92 ± 1.93 vs. 6.29 ± 1.80 mmol/l, P < 0.01). In conclusion, our results show a close association between the degree of insulin resistance and markers of oxidative stress, both before and after a high‐fat meal. The postprandial state causes an important increase in oxidative stress, especially in severely obese persons with greater insulin resistance. However, we are unable to determine from this study whether there is first an increase in oxidative stress or in insulin resistance.

Different effect of laparoscopic Roux-en-Y gastric bypass and open biliopancreatic diversion of Scopinaro on serum PYY and ghrelin levels.

BackgroundThe impact of bariatric surgery on levels of peptide YY (PYY) and ghrelin is still under discussion. We undertook a simultaneous evaluation of the serum changes in PYY and ghrelin depending on the specific type of bariatric surgery.MethodsTotal PYY and ghrelin were analyzed in 29 healthy persons and in morbidly obese persons undergoing open biliopancreatic diversion (BPD) of Scopinaro (n = 38) or laparoscopic Roux-en-Y gastric bypass (RYGB; n = 13).ResultsRYGB resulted in a significantly greater loss of weight and body mass index than BPD. Both RYGB and BPD were associated with a significant increase in PYY, significantly greater for BDP (p = 0.001). Ghrelin rose significantly after RYGB (p = 0.022) but not after BPD. After surgery, PYY correlated positively with weight (r = 0.416, p = 0.009). Ghrelin did not correlate significantly with any of the variables studied. Analysis of variance showed that only the type of surgery contributed significantly to explain the variances in the PYY (p = 0.002) and ghrelin (p = 0.018).ConclusionsBPD results in a greater increase in PYY and a lower weight loss than RYGB. However, only RYGB was associated with a significant increase in ghrelin. The differing weight loss according to the type of bariatric surgery does not seem to be explained by changes arising in PYY and ghrelin.

Obesity and Insulin Resistance-Related Changes in the Expression of Lipogenic and Lipolytic Genes in Morbidly Obese Subjects

BackgroundThe storage capacity of adipose tissue may be an important factor linking obesity, insulin resistance (IR), and associated morbidities. The aim of this study was to analyze the expression of lipogenic and lipolytic genes in adipose tissue and the influence of IR.MethodsWe studied the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) and lipogenic and lipolytic enzymes in the visceral (VAT) and subcutaneous adipose tissue (SAT) from 23 morbidly obese patients (MO; 13 with low IR and ten with high IR) and from 15 healthy, lean controls.ResultsIn the VAT and SAT from the MO, we found an increased expression of PPARγ (p = 0.001 and p = 0.022, respectively), acyl-coenzyme A (CoA)/cholesterol acyltransferase (p < 0.001 and p < 0.001), aquaporin 7 (p < 0.001 and p = 0.003), and adipose triglyceride lipase (p < 0.001 and p < 0.001) and a reduced expression of acetyl-coenzyme A carboxylase (p = 0.004 and p < 0.001), independently of the state of IR. The expression of phosphoenolpyruvate carboxykinase and acyl-CoA synthetase, however, was significantly lower in the MO with high IR (p < 0.05). Glycerol kinase (p = 0.010), hormone-sensitive lipase (p < 0.001), and perilipin (p = 0.006) were only significantly increased in VAT. Acyl-CoA synthetase (p = 0.012) and fatty acid binding protein-4 (p = 0.003) were only significantly decreased in SAT. The expression of the genes studied was only greater in the SAT than the VAT in the controls.ConclusionOur results show an upregulation of genes facilitating triglyceride/fatty acid cycling and a reduction in the genes involved in de novo synthesis of fatty acids in morbid obesity. The expression of some of the genes studied seems to be related with the state of IR. VAT and SAT differ metabolically and also between controls and MO.

Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects.

Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.

Bypass of the duodenum improves insulin resistance much more rapidly than sleeve gastrectomy

BACKGROUND Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitus and cardiovascular complications. Bariatric surgery is the most effective strategy for treating morbidly obese patients. We evaluated the metabolic changes that occur in the early stage after 2 types of bariatric surgery, biliopancreatic diversion of Scopinaro (BPD) and sleeve gastrectomy (SG), in morbidly obese patients. METHODS The study was undertaken in 31 nondiabetic morbidly obese patients (7 men and 24 women). Of the 31 patients, 18 underwent BPD and 13 underwent SG. All patients were examined before bariatric surgery (baseline) and at 15, 30, 45, and 90 days postoperatively. RESULTS Significant improvement occurred in the anthropometric variables after the 2 types of bariatric surgery, without significant differences between the 2 types of interventions. In patients undergoing BPD, the serum glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, and free fatty acids were significantly reduced. The changes that occurred in these biochemical variables after SG were not significant. Insulin resistance decreased significantly during the 90 days after surgery, with the greatest decrease at 15 days. However, in the patients who underwent SG, insulin resistance worsened at 15 days and later diminished. CONCLUSION The results of the present study have shown that the surgical technique that excludes the duodenum (i.e., BPD) has immediate postoperative changes in the degree of insulin resistance in morbidly obese patients compared to those techniques that do not exclude the duodenum (i.e., SG).

Plasma visfatin concentrations in severely obese subjects are increased after intestinal bypass

Objective: Visfatin has shown to be increased in obesity and in type 2 diabetes. The aim of this study was to determine the change in plasma visfatin in severely obese (SO) persons after weight loss following bariatric surgery in relation to glucose concentration.

La suplementación con ácidos grasos mejora parámetros respiratorios, inflamatorios y nutricionales en adultos con fibrosis quística

INTRODUCTION AND AIMS Chronic inflammation plays a major role in lung deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies have beneficial effects. To study the changes seen after a one-year course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation, pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), quality of life and anthropometric parameters. PATIENTS AND METHOD Seventeen adult subjects with CF received 324 mg of eicosapentaenoic, 216 mg of docosahexaenoic, 480 mg of linoleic and 258 mg of gammalinolenic acid daily. We assessed inflammation markers, spirometry parameters, number and severity of respiratory exacerbations, antibiotic consumption, quality of life (St Georges QoL), anthropometric parameters and serum phospholipid fatty acid composition. RESULTS At the end of the treatment period TNF alpha levels fell significantly and its soluble receptors (60 and 80) rose significantly. Levels of IgG and IgM anti-oxidized LDL antibodies fell significantly. Spirometry improved significantly. Annual respiratory exacerbations and days of antibiotic treatment fell significantly. The improvement in QoL was not significant. Serum levels of docosahexaenoic, total omega-3 and linoleic acid rose significantly and more favourable profiles were seen in monoenoic acids, arachidonic acid and the arachidonic/docosahexaenoic ratio. The fat-free mass and hand grip dynamometry improved significantly. CONCLUSIONS Low-dose supplements of n-3 and gammalinolenic fatty acids over a long period (one year) appears to improve pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), inflammatory and anthropometric parameters in adults with CF.

Fatty Acid Supplementation Improves Respiratory, Inflammatory and Nutritional Parameters in Adults with Cystic Fibrosis

Abstract Introduction and aims Chronic inflammation plays a major role in lung deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies have beneficial effects. To study the changes seen after a oneyear course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation, pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), quality of life and anthropometric parameters. Patients and method Seventeen adult subjects with CF received 324mg of eicosapentaenoic, 216mg of docosahexaenoic, 480mg of linoleic and 258mg of gammalinolenic acid daily. We assessed inflammation markers, spirometry parameters, number and severity of respiratory exacerbations, antibiotic consumption, quality of life (St Georges QoL), anthropometric parameters and serum phospholipid fatty acid composition. Results At the end of the treatment period TNF alpha levels fell significantly and its soluble receptors (60 and 80) rose significantly. Levels of IgG and IgM anti-oxidised LDL antibodies fell significantly. Spirometry improved significantly. Annual respiratory exacerbations and days of antibiotic treatment fell significantly. The improvement in QoL was not significant. Serum levels of docosahexaenoic, total omega-3 and linoleic acid rose significantly and more favourable profiles were seen in monoenoic acids, arachidonic acid and the arachidonic/docosahexaenoic ratio. The fat-free mass and hand grip dynamometry improved significantly. Conclusions Low-dose supplements of n-3 and gammalinolenic fatty acids over a long period (one year) appears to improve pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), inflammatory and anthropometric parameters in adults with CF.

Disruption of GIP/GIPR Axis in Human Adipose Tissue Is Linked to Obesity and Insulin Resistance

CONTEXT Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. OBJECTIVE Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. DESIGN GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. RESULTS GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. CONCLUSIONS GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

PPARγ Expression After a High-fat Meal Is Associated With Plasma Superoxide Dismutase Activity in Morbidly Obese Persons

Peroxisome proliferator‐activated receptor‐γ (PPARγ) may play a protective role in the regulation of vascular function, partly mediated by its effects on superoxide dismutase (SOD). The aim of this study was to determine the association between PPARγ expression in peripheral blood mononuclear cells (PBMCs) and SOD activity in morbidly obese persons with varying degrees of insulin resistance (IR). We studied in 10 morbidly obese persons (five with no IR and five with high IR) the effect of a high‐fat meal on the plasma activity of various antioxidant enzymes and the mRNA expression of PPARγ in PBMC. The high‐fat meal resulted in a significant decrease in plasma SOD activity, glutathione reductase (GSH‐Rd) activity, and mRNA expression of PPARγ only in the group of morbidly obese persons with high IR. PPARγ expression after the high‐fat meal correlated with the IR levels (r = −0.803, P = 0.009) and the plasma SOD activity (r = 0.903, P = 0.001). Likewise, the reduction in PPARγ expression correlated with the increase in free fatty acids (FFA) (r = 0.733, P = 0.016). In conclusion, the decreased expression of PPARγ in PBMC in morbidly obese persons after a high‐fat meal was associated with the state of IR, the plasma SOD activity, and the changes in the concentration of FFA.